Acute benign pleural effusion, a rare presentation of hepatitis A virus: a case report and review of the literature

Introduction Hepatitis A virus infections are mostly asymptomatic or mildly symptomatic, and generally this disease has a benign course and resolves spontaneously. However, intrahepatic and rarer extrahepatic manifestations can complicate typical cases of acute hepatitis. Pleural effusion is an extremely rare extrahepatic entity with 20 cases reported in literature. Case presentation We report herein a recent case of both pleural effusion and ascites accompanying hepatitis A infection in a 5-year-old middle eastern child, diagnosed using serological testing and imaging studies, who was treated with supportive management with full resolution after 2 weeks. In addition, we review available literature regarding hepatitis A virus associated with pleural effusion using PubMed and summarize all reported cases in a comprehensive table. Results Literature contains 20 reported cases of serology-confirmed hepatitis A virus presenting with pleural effusion, most in the pediatric population with average age at presentation of 9 years 8 months. The majority of reported patients had right-sided pleural effusion (50%) or bilateral effusion (45%), while only 5% presented with pleural effusion on the left side. Hepatomegaly and ascites occurred concurrently in 80% and 70% respectively. Supportive treatment without invasive procedures (except one chylothorax case) yielded complete recovery in 95% of cases, while only one case progressed to fulminant liver failure followed by death. Conclusion Acute hepatitis A virus rarely presents with pleural effusion, usually following a benign course with spontaneous resolution in most patients. Pleural effusion does not change the prognosis or require any invasive treatment. Thus, further invasive procedures are not recommended and would only complicate this self-resolving benign condition.


Introduction
Hepatitis A virus (HAV) is a positive-stranded Ribonucleic acid (RNA) virus that is stable at moderate temperatures and low pH, allowing for prolonged survival in the environment and fecal-oral transmission. It is known Open Access *Correspondence: Jihad.s.zalloum@gmail.com to circulate among children, especially in developing countries due to poor hygiene and lack of sanitation [1]. Although hepatitis A is usually asymptomatic or presents with mild symptoms in children, extrahepatic manifestations and, particularly, pleural effusions are rare [2,3]. The first case of pleural effusion caused by hepatitis A as underlying infection was described as early as 1971 by Gross and Gerding [4], but this association has been scarcely reported in medical literature, with no more than 20 cases [5]. We provide herein a comprehensive literature review of 20 published cases and also report a new case, to clarify this rare entity.

Case presentation
A previously healthy 5-year-old middle eastern boy with no known history of any medical diseases presented to the emergency department with jaundice and scleral icterus, in addition to dark-colored urine, abdominal pain and distention, and slight shortness of breath beginning 4 days previously after contact history with individuals having acute hepatitis A symptoms.
He had no previous history of traveling, blood transfusion, bleeding, or previous medical, drug, or surgical treatment.
Upon presentation, during physical examination, the patient had high fever (39 °C), abdominal distention, hepatomegaly with normal spleen size, unilateral basal right-sided decreased breathing sound and dullness, as well as tachycardia and tachypnea. The rest of the examination was normal, including normal mental status.
The patient was admitted, and laboratory investigations were carried out (Tables 1, 2). HAV serology testing was positive. Chest x-ray showed unilateral right-sided pleural effusion. Chest contrast computed tomography (CT) scan delineated right effusion with significant lung collapse, plus negligible amount on the left side and clear left lung field (Figs. 1, 2). Abdominal sonography and abdominal-pelvic CT scan identified hepatomegaly and ascites. Echocardiography was free of any abnormality.
Our patient was diagnosed with HAV acute hepatitis associated with right-side pleural effusion and ascites, confirmed by CT scan. Treatment consisted of supportive parenteral fluid and carbohydrate-enriched diet, while no diuretics or antibiotics were used. The patient was discharged on day 4 after significant improvement, achieving full clinical and biochemical recovery 5 days postdischarge with normal liver function tests and normal lung and abdominal imaging.

Discussion
Acute hepatitis caused by hepatitis A virus infection can manifest with a variety of symptoms and severities. One important factor is age, as disease severity is inversely proportional to age, with more than 80% of children having a less severe course and complete recovery within 3 months, usually being asymptomatic and anicteric. However, severity and mortality rates increase with advancing age [6].
Onset of symptoms follows a mean incubation period of approximately 30 days. Common signs and symptoms include fever, jaundice, fatigue, abdominal pain, nausea, and emesis.
Infectivity and viral shedding last from the beginning of the incubation period until 1 week after jaundice resolution, during which the virus is capable of fecal-oral spread [7].
HAV acute hepatitis may be associated with many complications, including:  1. Intrahepatic: such as cholestatic hepatitis, relapsing hepatitis, and autoimmune hepatitis. Rarely, hepatitis A can progress to acute liver failure.
Among those complications, pleural effusion is an extremely rare co-occurring condition that is scarcely reported in literature. The exact mechanism is unknown and could be multifactorial. There are many theories regarding the suspected pathogenesis of this entity:  [5,10]. 3. Also, a decrease in the plasma oncotic pressure as well as a transient rise of the pressure in the portal vein and/or lymphatics due to compression by the hepatic sinusoids may be a contributory factor in some cases developing ascites and pleural effusion [5,11].
Tables 3 and 4 present a comprehensive review of available published cases of HAV with pleural effusion. All 20 patients were diagnosed by positive serum anti-HAV IgM antibodies and pleural effusion on imaging studies, regardless of the underlying nature of effusion (transudative or exudative). Most patients were from the pediatric population with average age of 9 years 8 months, while 80% (16 patients) were younger than 12 years old, with a male-to-female ratio of 9:11. Most patients presented with usual symptoms of acute hepatitis including fever, vomiting, abdominal pain, jaundice, icterus, and fatigue. Also, abdominal and chest examination revealed hepatomegaly, abdominal distention, chest dullness, and decreased airway entry and normal mental status in all patients. Laboratory testing showed an average of 3.1 albumin g/dl, with average total and direct bilirubin of 5.2 and 4 mg/dl respectively. Chest x-ray, ultrasonography, and in some patients computerized tomography or magnetic resonance imaging all generally showed similar results: most patients had right-sided (ten patients) or bilateral pleural effusion (nine patients), while one case had effusion on the left side. Also, the majority copresented with hepatomegaly (16 patients) and ascites (14 patients). Finally, thickened gallbladder wall was seen in only three patients. Moreover, pleural fluid analysis mostly showed a transudative nature of the effusion, while one patient had exudative effusion resulting from Salmonella paratyphi A superinfection, and one case had     chylothorax, but pleural fluid analysis was carried out in a limited number of patients (nine). All patients were managed supportively. Furthermore, no invasive additional treatments were used in five cases, including intravenous fluids, vitamin K, oral lactulose, and antibiotics prophylactically for bacterial superinfection [12,14], while thoracostomy and chest tube insertion were only needed in one patient of chylothorax [13].
Of these patients, 95% (19 out of 20 patients) had complete recovery and resolution of pleural effusion and ascites, while one patient (5% of patients) suffered from fulminant liver failure and refractory intracranial pressure increase leading to death 2 weeks after diagnosis [14] HAV infection is usually self-limited and does not progress to a chronic or latent state, being managed supportively, and the same applies to associated pleural effusions. Pleural effusions do not change the prognosis or require any invasive treatment.

Conclusion
Pleural effusion is a benign, rare, extrahepatic complication of HAV acute hepatitis, mostly present in juveniles as early right-sided effusion. It resolves spontaneously with supportive management. Thus, further invasive procedures would only complicate this self-resolving benign condition and should be minimized.